Lack of protection against chemically induced injury to isolated hepatocytes by omission of calcium from the incubation medium.
Recent evidence has renewed interest in the hypothesis that Ca plays a central role in cell death. It was previously found that Cd and CuCl2 cause loss of viability of isolated hepatocytes. It was therefore of interest to determine whether Ca was intimately involved with the toxic effect of these metals. Some of the chemicals that were previously shown to be toxic through a mechanism involving Ca (amphotericin B, lysolecithin, and Ca ionophore A23187) were also included in the study. Hepatocytes were incubated with one of these chemicals and samples taken at various time points up to 120 min for estimation of cell viability (intracellular K+ and leakage of aspartate aminotransferase) and lipid peroxidation. The toxic effects due to Cd or Cu were not ameliorated on omission of Ca from the incubation medium. Furthermore, of the other three chemicals investigated, only the toxic properties of the Ca ionophore were effectively blocked by incubation in a Ca-free medium. The results of this study do not support the hypothesis that Ca plays a ubiquitous role in the death of liver cells.
D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002104:Cadmium / Q000633:toxicity; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000633:toxicity; D004347:Drug Interactions; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013858:Thiobarbiturates
D008054:Lipid Peroxides; D008244:Lysophosphatidylcholines; D013858:Thiobarbiturates; D002104:Cadmium; D000001:Calcimycin; D003300:Copper; D000666:Amphotericin B; D001219:Aspartate Aminotransferases; C029684:thiobarbituric acid; D011188:Potassium; C029892:cupric chloride; D002118:Calcium